There are more than 200 types of cancer, each with different causes, symptoms and treatments. Cancer is among the leading causes of morbidity and mortality worldwide. There were approximately 14.1 million new cases of cancer and 8.2 million cancer related deaths in 2012, with incidence rates varying across the world.
Cancer is the second leading cause of death in the United States, exceeded only by heart disease. In the United States in 2014, nearly 586,000 people are expected to die of cancer and more than 1.66 million new cancer cases are expected to be diagnosed, but the cost of cancer extends beyond the number of lives lost and new diagnoses each year. Cancer survivors, as well as their family members, friends, and caregivers, may face physical, emotional, social, and spiritual challenges as a result of their cancer diagnosis and treatment. The financial costs of cancer also are overwhelming. According to the National Institutes of Health, cancer cost the United States an estimated $263.8 billion in medical costs and lost productivity in 2010.
Hepatocellular carcinoma is one of the most lethal human cancers because of its high incidence and its metastatic potential, and it is among the most resistant to treatment. It is the third leading cause of cancer-related deaths worldwide.
Substantial research has been conducted worldwide, with limited success, in an effort to find effective treatments and/or a cure for cancer. The examples below describe some of those efforts, although the article in Molecules by M. Ismail, et al relates to the treatment of Alzheimer's disease, and the article by M. Raghuprasad, et al in the Asian Journal of Chemistry and the article by B. V. Ashalatha, et al in the European Journal of Medicinal Chemistry both relate to antimicrobial activity.
In a research paper by Rafat Mohareb and Abdelgawad Fahmy, titled Cytotoxicity of Novel 4,5,6,7-Tetrahydrobenzo[b]thiophene Derivatives and Their Uses As Anti-Leishmanial Agents, published in the European Chemical Bulletin, 2013, 2(8), 545-553, the authors studied the cytotoxicity of 4,5,6,7-tetrahydrobenzo[b]thiophene derivatives in the treatment of breast adenocarcinoma, non-small-cell lung cancer, and central nervous system lymphoma (CNS lymphoma). The compounds proposed by Mohareb and Fahmy all have a thiophene ring attached to the cyclohexene ring. The chemical structure is depicted in FIG. 1.
In a paper by Dhilli Gorja, Shiva Kumar, K. Mukkanti, and Manojit Pal, titled C—C(alkynylation) vs C—O (ether) Bond Formation Under Pd/C—Cu Catalysis; Synthesis and Pharmacological Evaluation of 4-Alkynylthieno[2,3-d]pyrimidines, published in the Journal of Organic Chemistry 2011, 7, 338-345, the authors proposed alkynyl substituted thienopyrimidines, notably 6-ethynylthieno[3,2-d]- and 6-ethynylthieno[2,3-d]pyrimidin-4-aniline derivatives useful in the treatment of leukemia. The authors used a Pd/C-Cul-PPh3 catalytic system to facilitate C—C bond formation between 4-chlorothieno[2,3-d]pyrimidines and terminal alkynes in methanol. A variety of 4-alkynylthieno[2,3-d]pyrimidines were prepared via alkynylation of 4-chlorothiene[2,3-d]pyrimidines. Such chemical structure is depicted in FIG. 2.
In an article titled Synthesis and Biological Evaluation of Thiophene Derivatives As Acetylcholinesterase Inhibors, published in Molecules 2012, 17, 7217-7231, Mohamed Ismail, Mona Kamel, Lamia Mohamed, Samar Faggal and Mai Galal proposed thiophene derivatives as acetylcholinesterase inhibitors useful in the treatment of Alzheimer's disease. The chemical structure is depicted in FIG. 3.
M. Raghuprasad, S. Mohan, B. Das and S. Srivastava published in the Asian Journal of Chemistry 2007; 19(5):2813-7, a paper titled Synthesis and Antimicrobial Activity of Some Thiadiazolo Thienopyrimidines, in which thiadiazolo thienopyrimidin derivatives are attached with cyclohexene ring and the benzene ring is attached with methoxy group (—OCH3), but do not have a carbonyl group (C═O) nor is a benzene ring attached with a nitro group (—NO2). The biological objective in their paper was antimicrobial activity. The chemical structure is depicted in FIG. 4.
B. V. Ashalatha, B. Narayana, K. K Raj Vijaya and S. Kumari published in the European Journal of Medicinal Chemistry 2007, 42, 719-728, a paper titled Synthesis of Some New Bioactive 3-Amino-2-mercabto-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-one Derivatives, in which their compounds have thiadiazolo thienopyrimidin derivatives attached with cyclohexene ring. The compound is not attached with a cycloheptene ring. Their biological objective was antimicrobial, anti-inflammatory, anticonvulsant and neuropsychobehavioural effects. The chemical structure is depicted in FIG. 5.
V. Alagarsamy, U.S. Pathak, V. Rajasolomon, S. Meena, K. V. Ramseshu, and R. Rajesh published in the Indian Journal of Heterocyclic Chemistry 2004; 13; 347. 2004; 13; 347 an article titled Anticancer, Antibacterial and Antifungal Activities Of Some 2-substituted(1,3,4)thiadiazolo(2,3-b)tetrahydrobenzo(b)thieno(3,2-e)pyrimidines, wherein they synthesized (1,3,4) thiadiazole(2,3-b)tetrahydro-benzothieno[3,2-e]pyrimidines and then screened them for anticancer, antibacterial and antifungal activities. Their compounds have thiadiazolo thienopyrimidin derivatives attached with cyclohexene ring. The compound is not attached with cycloheptene ring. Their objectives are anticancer, antibacterial and antifungal. The chemical structure is depicted in FIG. 6.
Drugs have been developed that produce favorable results in some cancers that are more susceptible to treatment, but no really effective drug has been developed for the treatment of hepatocellular carcinoma. The compounds mentioned in the articles noted above have limited, if any, effectiveness in the treatment of liver cancer.
Accordingly, there is a need for a treatment that is more effective in reducing the growth and propagation of human liver cancer cells (HepG2).